Pregabalin (PGB) in treatment of oxaliplatin-induced neuropathy

Abstract

e15045 Background: Oxaliplatin is effective in many GI cancers, especially colorectal cancer (CRC); however, severe neuropathy develops frequently. PGB is a new antiepileptic drug approved as adjunctive therapy of partial seizures in adults, pain from diabetic neuropathy and post-herpetic neuralgia. PGB is structurally related to gabapentin, but unlike gabapentin, it is well absorbed (> 90%) and its absorption is dose independent. In this study, we evaluated the role of PGB in reduction of oxaliplatin- induced neuropathy. Methods: From Nov 2006 to Dec 2008, a total of 23 pts (age range: 50–71 yrs; M:F = 14:9) with GI cancers were treated with PGB upon development of oxaliplatin-induced neuropathy > G2 (NCI-CTC 3.0). Of these pts, 15 received FOLFOX for CRC, 2 EOX for gastric ca and 6 GemOx for pancreatic ca. Neurologic symptoms were evaluated prior PGB and then q 2 wks. PGB was started at 50mg PO tid, and if tolerated, dose was escalated by 50mg increments until symptoms improved up to a maximum of 150mg PO tid. Results: 5/23 pts (22%) were escalated to 150mg PO tid. 12 pts (52%) were escalated to 100mg tid, out of which 7 (58%) continued, 4 (33%) stopped due to no benefit and 1 (8%) stopped due to weight gain. 1/23 (4%) decided to follow 100mg bid. 5/23 (22%) could not be escalated above 50mg tid; 2 continued at this dose and 3 stopped due to CNS side effects. Onset of benefit was observed in 2 - 6 wks. In 3/23 pts (13%), neuropathy improved from G3 to G2, 2/23 (9%) from G3 to G1, 5/23 (22%) from G2 to G1, 6/23 (26%) remained stable at G2 and no pts remained at G3. Most pts continued PGB even beyond disease progression on oxaliplatin (15/23). Among those who continued (15), duration of therapy was 4 -24 months. The best benefit with PGB was seen at a dose of 150mg tid, followed by 100mg tid. The most common non-hematologic toxicities were dizziness (57%), headache (26%), somnolence (22%), dry mouth (17%), ataxia (17%), tremor (13%), peripheral edema (13%), weight gain (13%), blurred vision (13%) and constipation (9%). Hematologic toxicity (G1 thrombocytopenia) was seen in 1 pt (4%) but impact of chemotherapy could not be excluded. Conclusions: PGB significantly reduces the severity of oxaliplatin-induced neuropathy. Larger, placebo-controlled trials assessing safety and efficacy of oral PGB are warranted in pts treated with oxaliplatin. [Table: see text]